What is Autophagy?
Autophagy, a term derived from the Greek words for "self" and "eating," refers to the process by which cells degrade and recycle their own components along with viruses and bacteria.
This vital process helps to clear damaged or dysfunctional proteins and organelles from cells, enabling the efficient function of bodily tissues and organs. It also plays a crucial role in cellular repair and detoxification, contributing to better health and potentially prolonging lifespan.
The 2016 Nobel Prize in Physiology or Medicine was awarded to Yoshinori Ohsumi for discovering the mechanisms of autophagy in the 1990s. 1
How does autophagy work?
Autophagy is an evolutionarily conserved process, which means the gene that controls autophagy has remained essentially unchanged throughout evolution. 2
There are three main types of autophagy that are critical to maintain the health of the cells:
Microautophagy involves the direct engulfment of bacteria and viruses.
Chaperone-mediated autophagy (CMA) targets soluble proteins. These are recognised by heat shock proteins which help to spot these proteins. Heat shock proteins are derived from exposure to high heat, like saunas.
Macroautophagy, commonly known as autophagy, is the most studied type, involving the engulfment of poor functioning cargo and then degradation or recycling of it. 3
How Do You Stimulate Autophagy?
Stimulating autophagy is a topic of great interest due to its implications for health and longevity. There are several ways to induce this process:
Caloric Restriction: Limiting calorie intake without malnutrition stimulates autophagy as cells need to recycle components to sustain their functions in the absence of external nutrients. This is generally defined as a 10–40% reduction in caloric intake. 4
Intermittent Fasting: This involves alternating periods of eating and fasting. It is not just about reducing calories but also about extending the periods when the body is not processing food, which encourages cells to initiate autophagy.
Exercise: Regular physical activity can induce autophagy in various organs such as the muscles, liver, and brain. This is thought to be due to the increased energy and repair demands placed on cells during and after exercise.
Protein Restriction: Reducing protein intake after an activity can also trigger autophagy since protein deprivation signals a need to recycle internal proteins for essential biological processes. Protein should be reduced to around 25g to 30g a day.
Consumption of Autophagy-Inducing Compounds: Certain compounds found in foods like turmeric (curcumin), green tea (epigallocatechin gallate), and coffee (caffeine) have been found to stimulate autophagy.
Low-carb, High-Fat Diets: A ‘Keto diet’ changes the way your body burns energy, so that instead of burning carbs or sugar for energy, it burns fat instead. Glucose deprivation and the consequent alterations in energy charge and stress levels (Reactive Oxygen Species) are potent activators of autophagy.
How to Fast For Autophagy.
Fasting plays a significant role in inducing autophagy, particularly through intermittent fasting or time-restricted eating patterns. When you fast, the decrease in external nutrient levels triggers cellular stress responses, which include autophagy. This process begins to significantly increase as your liver glycogen stores deplete, generally 12 to 16 hours after beginning a fast. Lowered insulin triggers increased glucagon, the body’s naturally produced hormone which can help stabilise blood sugar levels. The presence of this hormone signals the need for autophagy.
Research shows that a 18 hour overnight intermittent fasts coupled with low protein days (MAX 25g of protein following the fast) can increase autophagy by 22% in the morning
Protocol:
1. Choose three non-consecutive low protein days
2. Fast overnight and into the morning (for a total of 18 hours or more) - Last meal at 17:00 then eat again at 11:00 the following day.
3. Limit your protein intake following your fast to 25 grams all day.
How Long After You Start Fasting Does Autophagy Start?
The answer is, there is no ‘switch’ because it depends on other factors such as your environment, protein intake, if you have exercised. Research suggests that markers of autophagy are observed to increase in human cells anywhere between 18 and 48 hours after the start of a fast. The exact onset time can vary based on individual metabolism, previous diet, and overall health as we mentioned.
What Breaks Autophagy?
We do not exactly know and it will vary from person to person. Consuming any calories could potentially break autophagy. If calories are consumed from fat, it is less likely to affect it as a ketogenic state can induce autophagy. However, eating particularly carbohydrates or proteins, can halt autophagy. This is because the intake of nutrients activates signalling pathways (like mTOR) that suppress the autophagy process. Thus, maintaining periods of fasting or adhering to specific diets low in protein can help sustain autophagy.
Other Aspects That Help Induce Autophagy
Besides fasting and dietary measures, other factors can also induce autophagy:
Adequate Sleep: Poor sleep can disrupt cellular processes including autophagy. Ensuring enough quality sleep helps maintain the body’s natural rhythms, including those governing cell repair and cleanup.
Stress Management: Stress, particularly oxidative stress, can trigger autophagy as a defensive response to cell damage. Practices that reduce oxidative stress, like mindfulness and moderate exercise, can support autophagy.
Cooler Temperatures: Exposure to cold can stimulate autophagy as cells activate this process to produce energy and maintain body heat.
Ground Rules for Autophagy
To effectively induce autophagy, consider these ground rules:
Understand your body’s cues: Pay attention to how your body responds to different stimuli like fasting or dietary changes. You might be doing long fasts, low protein but getting poor sleep. Take a holistic approach to get better outcomes.
Balance is key: While autophagy has many benefits, overstimulating it through excessive fasting or extreme dietary restrictions can be counterproductive and harmful.
Age: Younger individuals naturally have more robust autophagic activity compared to older adults, in whom the process becomes less efficient. Older adults may benefit from more frequent induction of autophagy to help counteract the aging process.
Conclusion
Autophagy is a complex but fascinating process that plays a vital role in maintaining cellular health and function. By understanding how to naturally stimulate autophagy through methods like fasting, exercise, and diet modification, you can potentially enhance your body's ability to heal and rejuvenate itself. With the right balance and awareness, harnessing the power of autophagy can be an integral part of a holistic approach to health and longevity.
References:
1. Tsukada M, Ohsumi Y. Isolation and characterization of autophagy-defective mutants of Saccharomyces cerevisiae. FEBS Lett. 1993;333((1-2)):169–74. doi: 10.1016/0014-5793(93)80398-E.
Antunes F, Erustes AG, Costa AJ, Nascimento AC, Bincoletto C, Ureshino RP, Pereira GJS, Smaili SS. Autophagy and intermittent fasting: the connection for cancer therapy? Clinics (Sao Paulo). 2018 Dec 10;73(suppl 1):e814s. doi: 10.6061/clinics/2018/e814s. PMID: 30540126; PMCID: PMC6257056.
Jamshed, H.; Beyl, R.A.; Della Manna, D.L.; Yang, E.S.; Ravussin, E.; Peterson, C.M. Early Time-Restricted Feeding Improves 24-Hour Glucose Levels and Affects Markers of the Circadian Clock, Aging, and Autophagy in Humans. Nutrients 2019, 11, 1234. https://doi.org/10.3390/nu11061234
Mohammad Bagherniya, Alexandra E. Butler, George E. Barreto, Amirhossein Sahebkar,. The effect of fasting or calorie restriction on autophagy induction: A review of the literature,Volume 47, 2018, Pages 183-197,ISSN 1568-1637, https://doi.org/10.1016/j.arr.2018.08.004. (https://www.sciencedirect.com/science/article/pii/S1568163718301478)
Mayor E. Neurotrophic effects of intermittent fasting, calorie restriction and exercise: a review and annotated bibliography. Front Aging. 2023 Jun 2;4:1161814. doi: 10.3389/fragi.2023.1161814. PMID: 37334045; PMCID: PMC10273285.
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